CDCP1

Chr 3

CUB domain containing protein 1

Also known as: CD318, SIMA135, TRASK

This gene encodes a transmembrane protein containing three extracellular CUB domains that functions as a substrate for Src family kinases and is involved in cell adhesion and cell-matrix interactions. The gene is highly constrained against loss-of-function variants (pLI near 1, LOEUF 0.65), but no established Mendelian diseases have been associated with CDCP1 mutations in pediatric populations. Current evidence suggests its primary relevance is in oncology rather than developmental neurological disorders.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.65
Clinical SummaryCDCP1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 unique Pathogenic / Likely Pathogenic· 111 VUS of 140 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.65LOEUF
pLI 0.000
Z-score 3.03
OE 0.40 (0.260.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.37Z-score
OE missense 0.82 (0.760.90)
395 obs / 479.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.40 (0.260.65)
00.351.4
Missense OE0.82 (0.760.90)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 12 / 29.8Missense obs/exp: 395 / 479.6Syn Z: 0.84
DN
0.6259th %ile
GOF
0.5071th %ile
LOF
0.3357th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

140 submitted variants in ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS111
Likely Benign6
Benign3
7
Pathogenic
1
Likely Pathogenic
111
VUS
6
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
1
0
1
VUS
1
108
2
0
111
Likely Benign
0
6
0
0
6
Benign
0
2
0
1
3
Total1116101128

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CDCP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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